Project 3: Pathophysiology of human age-related hearing loss

项目3：人类年龄相关性听力损失的病理生理学

• 批准号: 10018502
• 负责人: KELLY C HARRIS
• 金额: $ 35.03万
• 依托单位: MEDICAL UNIVERSITY OF SOUTH CAROLINA
• 依托单位国家: 美国
• 财政年份: 1997
• 资助国家: 美国
• 起止时间: 1997-07-01 至
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10018502
• 关键词: Acoustic Nerve; Action Potentials; Activities of Daily Living; Age; Aging; Amplifiers; Anatomy; Animal Model; Auditory; Autopsy; Cells; Characteristics; Classification; Clinical Research; Clinical Trials; Cochlea; Cochlear Nerve; Communication; Complex; Databases; Detection; Diagnostic tests; Dimensions; Elderly; Electroencephalography; Environmental Exposure; Fiber; Functional disorder; Genetic; Goals; Hearing; Hearing Tests; Heterogeneity; High Prevalence; Human; Imaging Techniques; Individual; Individual Differences; Intervention; Labyrinth; Lateral; Lead; Link; Measures; Metabolic; Methods; Morphology; Mutant Strains Mice; Nerve Fibers; Noise; Outer Hair Cells; Participant; Pathologic; Pathology; Pattern; Phenotype; Physiological; Predisposition; Presbycusis; Public Health; Recording of previous events; Sensory; Site; Source; Speech; Stria Vascularis; Structure; Symptoms; Temporal bone structure; Testing; Variant; age related; auditory processing; base; cognitive function; comorbidity; experimental study; functional decline; hearing impairment; human subject; improved; individualized medicine; mouse model; novel; otoacoustic emission; preservation; relating to nervous system; speech recognition; voltage

PROJECT SUMMARY/ABSTRACT – PROJECT 3 Determining the mechanisms and site(s) of pathologies involved in age-related hearing loss is challenging as they likely reflect a lifetime of environmental exposures, differences in susceptibility and co- morbidities, and complex genetic factors. These individual differences may contribute to the large variation in audiometric profiles and suprathreshold auditory function seen in older adults. In our Center, classification of metabolic and sensory presbyacusis phenotypes is based on animal models linking specific cochlear deficits to audiometric profiles, and has resulted in four cochlear-based phenotypes. Project 3 will refine these phenotypes by developing and validating physiologic measures that predict cochlear and auditory nerve pathology in older adults. Aim 3.1 tests the hypothesis that outer hair cell and cochlear lateral wall deficits differentially contribute to sensory versus metabolic presbyacusis. Experiments in Aim 3.1 incorporate metrics related to outer hair cell and stria vascularis function to predict cochlear pathologic site(s) and determine the extent to which patterns of pathology are consistent with estimates of sensory and metabolic hearing loss. Aim 3.2 examines auditory nerve structure and function to test the hypothesis that changes in auditory nerve activity result in unique and additive effects in auditory function of older adults. By using similar physiologic assessments, experiments in Project 1 and Project 2 will provide a means to validate Project 3 results in mouse models where the mechanisms and anatomical pathology are well defined. A significant advancement in the characterization of underlying cochlear and neural pathologies of presbyacusis is crucial in developing and testing new treatments as they become available, by appropriately assigning participants in clinical trials, and in determining the best course of intervention for an individual. Moreover, individual differences in pathophysiology identified in Project 3 are hypothesized to have differential effects on cortical representation of speech and suprathreshold auditory processing, assessed in Project 4.

项目摘要/摘要 – 项目 3 确定与年龄相关的听力损失相关的病理机制和部位 具有挑战性，因为它们可能反映了一生的环境暴露、敏感性和共同性的差异 发病率和复杂的遗传因素可能导致巨大的差异。 在我们的中心，老年人的听力特征和阈上听觉功能的分类。 代谢性和感觉性老年性耳聋表型基于动物模型，将特定的耳蜗缺陷与 听力特征，并产生了四种基于耳蜗的表型，项目 3 将完善这些特征。 通过开发和验证预测耳蜗和听觉神经的生理测量来确定表型 目标 3.1 检验外毛细胞和耳蜗侧壁缺陷的假设。 目标 3.1 中的实验纳入了指标，对感觉性老年性耳聋和代谢性老年性耳聋的影响有所不同。 与外毛细胞和血管纹功能相关，可预测耳蜗病理部位并确定 病理模式与感觉和代谢性听力损失的估计一致的程度。 3.2 检查听神经结构和功能，检验听神经变化的假设 通过使用类似的生理机制，活动会对老年人的听觉功能产生独特和附加的影响。 项目 1 和项目 2 中的评估、实验将提供验证项目 3 结果的方法 机制和解剖病理学得到明确定义的小鼠模型是一项重大进步。 老年性耳聋的潜在耳蜗和神经病理学特征对于发展至关重要 并通过在临床试验中适当分配来测试新的治疗方法， 此外，在确定针对个体的最佳干预方案时，个体差异也存在。 项目 3 中确定的病理生理学被重新捕获，对皮质表征有不同的影响 言语和阈上听觉处理的能力，在项目 4 中评估。